Satoh Wataru, Gotoh Takafumi, Tsunematsu Yasuhiko, Aizawa Shinichi, Shimono Akihiko
Vertebrate Body Plan, Center for Developmental Biology, RIKEN Kobe, Chuou-ku, Kobe 650-0047, Japan.
Development. 2006 Mar;133(6):989-99. doi: 10.1242/dev.02274. Epub 2006 Feb 8.
Regulation of Wnt signaling is essential for embryonic patterning. Sfrps are secreted Wnt antagonists that directly interact with the Wnt ligand to inhibit signaling. Here, we show that Sfrp1 and Sfrp2 are required for anteroposterior (AP) axis elongation and somitogenesis in the thoracic region during mouse embryogenesis. Double homozygous mutations in Sfrp1 and Sfrp2 lead to severe shortening of the thoracic region. By contrast, a homozygous mutation in one or the other exerts no effect on embryogenesis, indicating that Sfrp1 and Sfrp2 are functionally redundant. The defect of a shortened thoracic region appears to be the consequence of AP axis reduction and incomplete somite segmentation. The reduction in the AP axis is partially due to abnormalities in cell migration of pre-somitic mesoderm from the end of gastrulation. Aberrant somite segmentation is associated with altered oscillations of Notch signaling, as evidenced by abnormal Lfng and Hes7 expression during somitogenesis in the thoracic region. This study suggests that Wnt regulation by Sfrp1 and Sfrp2 is required for embryonic patterning.
Wnt信号通路的调控对于胚胎模式形成至关重要。分泌型卷曲相关蛋白（Sfrps）是Wnt拮抗剂，可直接与Wnt配体相互作用以抑制信号传导。在此，我们表明，在小鼠胚胎发育过程中，Sfrp1和Sfrp2是胸段前后轴（AP）伸长和体节发生所必需的。Sfrp1和Sfrp2的双纯合突变导致胸段严重缩短。相比之下，其中一个基因的纯合突变对胚胎发育没有影响，这表明Sfrp1和Sfrp2在功能上是冗余的。胸段缩短的缺陷似乎是AP轴缩短和体节分割不完全的结果。AP轴的缩短部分是由于原肠胚形成末期前体节中胚层细胞迁移异常所致。异常的体节分割与Notch信号通路振荡改变有关，胸段体节发生过程中Lfng和Hes7表达异常证明了这一点。这项研究表明，Sfrp1和Sfrp2对Wnt的调控是胚胎模式形成所必需的。
